P869: PRODUCTION BY GUT MICROBIOTA AS PROGNOSTIC BIOMARKER IN MM
Authors: A. Rodríguez-García, R. Garcia-Vicente, M. L. Morales, R. Gómez-Gordo, P. Justo, C. Cuéllar, J. Sánchez-Pina, D. Gómez-Garre, J. Martínez-López, M. Linares
Journal: HemaSphere (2022)

Background: There is increasing evidence compelling that the microbiota has a strong impact on cancer. The presence of these microorganisms and their activity could have an impact on immune cells and the bone marrow, playing an important role in the progression of multiple myeloma (MM). The short-chain fatty acids (SCFAs) metabolites from gut microbiota have been linked to beneficial effect in the response of MM to treatment. Aims: In this work we explore whether microorganisms and metabolites of the gut microbiota are imbalanced in monoclonal gammopathies and their possible role in the development of MM. Methods: We collected 51 patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 12), smoldering (SMO) (n=7) and MM at diagnosis (MMdx) (n = 11), at relapse (MMrf) (n=7) and at complete remission (CR) (n = 7, 3 of them paired with their diagnostic stage). Furthermore, healthy patients (n = 8) were included as controls (C). After the extraction of the microbial DNA from fecal samples, the ribosomal subunit of the bacterial 16S gene was sequenced on the Illumina® MiSeq ™ and bioinformatic analysis and quantification of absolute abundance were carried out. The analysis of metabolites released by the gut bacteria was performed by the quantification of SCFAs acetate, butyrate and propionate on serum samples by MRM (LC-QQQ-MS). The effect of SCFAs on the proliferation of human MM tumor cell lines was evaluated using standard MTT assays. Results: Patients with MMrf showed the lowest estimated richness with significant differences in Alpha diversity measured by Pielou’s index (Fig 1A). Beta diversity clustered separately and was significant in patients with MM at complete remission compared to MMdx in paired samples (Fig. 1B). Then, we compare the taxonomic composition of the gut microbiota of patients at different stages of the disease, and we found significant differences in the relative abundance of some microorganisms. On one hand, the genus Butyricimonas decreased in MM and its preclinical stages compared to controls and the genus Blautia was lower at MMdx compared to MMcr patients. Both microorganisms are butyrate producers which suggests a possible beneficial role of these microorganisms. In contrast, some genus such as Lachnoclostridium were increased in MMdx (Fig. 1C). To delve into the functional profiles of the microbial communities, we predicted metabolic pathways based on taxonomic profiles and we observed an increased in pathways involving the SCFA propionate in MMcr compared to MMrf (Fig. 1D). The SCFA butyrate was found decreased in MMdx compared with MGUS patients in serum levels (Fig. 1E). The in vitro assays with MM cell lines showed that the SCFAs acetate, butyrate and propionate had an antiproliferative effect (Fig. 1E). Image:Summary/Conclusion: Our study showed differences in the abundance levels of gut microbiota both on the progression and the response of the MM disease. The presence of some microorganisms and their metabolites, such as SCFAs, suggests a beneficial role which could be exploited as biomarkers of prognosis.